The present disclosure is directed towards diabetes therapy systems as used in the therapy of diabetes mellitus by Continuous Subcutaneous Insulin Infusion (CSII) and control units for a pump unit of such systems.
The present disclosure is further directed towards methods for controlling operation of an pump unit in such a system.
Continuous Subcutaneous Insulin Infusion (CSII) is an advanced and therapeutically advantageous way of treating diabetes mellitus. Under CSII, a diabetic carries a miniaturized infusion pump substantially continuously, night and day. The infusion pump infuses minimal quantities of insulin in a substantially continuous way according to a person-specific, generally time-variable infusion schedule, thus providing a so-called basal amount of insulin that is required by the diabetic's body for maintaining a normal or close-to-normal metabolism and in particular glucose concentration. For typical state-of-the-art systems, the basal administration schedule follows a generally circadian cycle and is preset by a healthcare professional. In addition, insulin pumps are designed to administer larger insulin quantities, so called boli, within a short period of time on demand, in order to cover diabetic's food intake, and under exceptional circumstances, such as illness or in case of a hyperglycaemia (also referred to as hyperglycaemic excursion or hyperglycaemic episode), which is a situation of increased glucose concentration, resulting from a relative lack of insulin within the diabetic's body.
Here and following in the present disclosure, “glucose” and phrases like “glucose value” or “glucose concentration” refer to glucose measured in a diabetic's blood, i.e., glucose, or glucose that is correlated with the glucose, in particular glucose in the subcutaneous tissue or interstitial fluid.
The opposite to a situation of hyperglycaemia is a hypoglycaemia (also referred to as hypoglycaemic excursion or hypoglycaemic episode), where the glucose level is too low, i.e., below a generally desired level, resulting from a relative excess of insulin within the diabetic's body. Both hyperglycaemia and hypoglycaemia may, when not appropriately dealt with, result in severe and potentially fatal complications. Untreated hypoglycaemia may in particular lead, within minutes to few hours, to symptoms and behaviour generally known for and associated with drunkenness or drug consumption, followed by a hypoglycaemic coma and finally death. During everyday life, the potential embarrassment that may result from hypoglycaemic symptoms is a constant source of concern and causes considerable psychological stress to many diabetics. In situations where full ability to react, motor capabilities and general awareness is crucial, like in some sports or when driving a car, hypoglycaemias may lead to potentially fatal accidents. The nocturnal sleep is a serious source of concern for many diabetics because the hypoglycaemia awareness of many diabetics is disabled or largely reduced in this time period.
In order to generally monitor correct operation of the insulin pump and to allow appropriate reaction in case of exceptional circumstances, such as hyperglycaemic or hypoglycaemic excursions, diabetics on CSII therapy need to test their glucose level at least several times a day, typically using glucose meters based on invasive (finger-prick) spot measurements of the glucose and/or, in recent times, using a Continuous Glucose Monitor (CGM), typically measuring glucose in the interstitial tissue.
While requiring considerable technical effort as well as constant awareness of the diabetic (or a person such as a relative), CSII therapy allows maintaining the diabetic's metabolism and in particular his or her glucose level in a close-to-normal range in everyday life. There is, however, a general concern with respect to the awareness of and appropriate reaction on hypoglycaemias as explained before.
To cope, among others, with such situations, closed-loop-systems (also known as Artificial Pancreas (AP)), have been under development for many years now, in which a CGM is operatively coupled to an insulin pump via a control algorithm in order to automatically ensure appropriate insulin infusion. Because of its high costs, technical complexity and safety concerns, however, no such systems are commercially available or in routine use.
With recent improvements in the development of CGM systems, however, Low Glucose Suspend (LGS) systems have become available. In such a system, an insulin pump is generally operated and infuses basal insulin like in standard CSII therapy according to a preset infusion schedule. A CGM, however, is additionally present and coupled to the control unit of the insulin pump. In case of the occurrence of a hypoglycaemia—detected by the glucose level falling below a low shutoff threshold—the pump is automatically shut off, resulting in insulin infusion being suspended, and a warning or alarm is provided. Infusion according to the schedule may be resumed automatically after a preset suspend time, of, e.g., 2 h, upon the glucose level rising above the threshold, or manually by the diabetic after resolving the situation. Such a system is disclosed in WO 2006/083831 A1, a commercial system is known as MiniMed Paradigm VEO by Medtronic MiniMed, Inc.
In practice, however, the advantages of systems as described above is limited by drawbacks that at least significantly reduce the practical value. Current LGS or similar approaches act in a static way, based on pre-programmed glucose thresholds. In order to safely prevent nocturnal hypoglycaemia, the low shutoff threshold is typically set to a comparatively high glucose level, the occurrence of which would generally not be a reason for concern as long as the diabetic is awake and conscious. A considerable number of erroneous shutoffs or “false alarms” is therefore known to occur. In addition, a fixed shutoff threshold is not considered to be appropriate in all situations. During daytime, an office worker may, for example, be willing to accept or even strive at comparatively low glucose levels in order to avoid long-term complications that are known to be associated with frequent hyperglycaemias. In a business meeting or when driving a car, she or he may whish to ensure a somewhat higher glucose level to safely avoid hypoglycaemias where—at the best—concentration, the ability to respond, and the general motor behaviour are aversively affected, while a moderate hyperglycaemia causes by far less concern when occurring occasionally and for a comparatively short time period only.